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α7nAChR inhibition by methyllycaconitine citrate promotes cell pyroptosis by triggering the polyol pathway in cervical cancer cells

JUNYING XU1,#, PING LI1,#, GE WANG2, DAQIANG YE1,*, XIUFU TANG3,*

1 Department of Gynecology, Zhuhai Women’s and Children’s Hospital, Zhuhai, 519000, China
2 Institute of Genetic Research, Zhuhai Women’s and Children’s Hospital, Zhuhai, 519000, China
3 Department of Pediatric Haematology and Rheumatalogy, Zhuhai Center For Maternal and Child Health Care, Zhuhai, 519000, China

* Corresponding Authors: DAQIANG YE. Email: email; XIUFU TANG. Email: email

BIOCELL 2024, 48(2), 283-291. https://doi.org/10.32604/biocell.2023.045429

Abstract

Background: α7 nicotinic acetylcholine receptor (α7nAChR) has been demonstrated to be involved in numerous of inflammatory diseases. Cell pyroptosis is a kind of cell death accompanied by inflammation. Objectives: The objective of this work is to explore the function of α7nAChR on cell pyroptosis in cervical cancer cells. Methods: Immunoblotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay were employed to examine the function of α7nAChR on cell pyroptosis and metabolic changes. Results: Herein, we found that α7nAChR inhibition led to cell pyroptosis in HeLa and SiHa of cervical cancer cells, which was attributed to the upregulation of the polyol pathway. Inhibition of α7nAChR in HeLa and SiHa cells induced the activation of NACHT, LRR and PYD domains-containing protein 3 inflammasomes, leading to enhanced cleaved caspase-1 expression to activate gasdermin D and interleukin-18/1β mature and secretion. Moreover, α7nAChR activation in cervical cancer cells decreased the aldo-keto reductase family 1 member B1 (AKR1B1)-mediated polyol pathway, resulting in reduced sorbitol production. Suppression of AKR1B1 could overcome cell pyroptosis caused by α7nAChR inhibition. Mechanically, α7nAChR inhibition could increase the level of phosphorylation of nuclear factor-kappa B (NF-κB) in HeLa cells, while α7nAChR activation caused inhibition of NF-κB phosphorylation, which further reduced NF-κB binding to the AKR1B1 promoter and consequently abolished AKR1B1 transactivation. In addition, inhibition of NF-κB activity could reverse the promotion of α7nAChR inhibition on cell pyroptosis. Conclusion: This work enriches the metabolic function of α7nAChR in cancer cells and reveals the novel mechanism of α7nAChR-mediated cell pyroptosis.

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Cite This Article

XU, J., LI, P., WANG, G., YE, D., TANG, X. (2024). α7nAChR inhibition by methyllycaconitine citrate promotes cell pyroptosis by triggering the polyol pathway in cervical cancer cells. BIOCELL, 48(2), 283–291.



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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